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    Identification and Biochemical Characterization of Novel Inhibitors of Nonhomologous End Joining: Implications in DNA Double-Strand Break Repair and Cancer Therapy

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    Author
    Ray, Ujjayinee
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    Abstract
    To summarize, in the present study, we have synthesized and characterized three novel NHEJ inhibitors targeting DNA Ligase IV, with several fold better efficacy compared to SCR7 and thus potential to be developed as cancer therapeutic agents. While SCR130 showed up to 22-fold better efficacy, compounds A and B exhibited >100 fold better cytotoxicity in cancer cell lines. First level preclinical studies reveal that novel inhibitors, A and B are interesting molecules and could be used in clinical trials for targeted therapy, particularly by a combinatorial mode. Considering that there is no drug currently used in clinic that target DNA double-strand break repair, these NHEJ inhibitors could be developed as cancer therapeutics against cancers with higher expression of Ligase IV, as well as against radio- and chemoresistant cancers
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    https://etd.iisc.ac.in/handle/2005/5193
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    • Biochemistry (BC) [259]

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